Secondary Outcomes
a. Acute asthma severity score in ED and hospitalized studies:Although all the studies included information for this outcome, they were analyzed separately according to the setting, type of score, and how it was reported. The two big trials23,25 done in the ED included difference in score, without giving the basal or post-intervention score, precluding the possibility to include their data in the overall score meta-analysis of ED studies. There was no significant difference in the asthma score between the budesonide and the control group in these two trials (Figure 5a). This result was similar using random effect model (RR=-0.13 [-0.38 to 0.12), p=0.30). The other four studies done in ED20,22,27,28 reported post-intervention data; when the data was reported in median and IQR, we estimated mean and SD according to the literature16. We found that children from the budesonide group significantly improved their asthma score compared with the placebo group in the ED studies20,22,27,28 (SMD: -0.30 [-0.53 to -0.06], p=0.01, I2=27%), Figure 5b. This result was similar using random effect model (SMD: -0.31 [-0.60 to -0.02), p=0.04). In the subanalysis comparing doses of budesonide (≥2mg vs. <2 mg), the pool data of ED studies showed a significant improvement in acute asthma severity score in the budesonide vs. placebo group, but clearly this effect was driven by the studies using ≥2 mg (Figure 5c).
Among studies performed in trials with hospitalized children, one study24 showed a significant differences in the asthma score at 1 hour, 2 hours and 3 hours from intervention favor to budesonide vs placebo group (7.36±1.03 vs 9.18±1.01 p<0.01 at 1h, 5.91±0.52 vs 7.30±1.05 p<0.01 at 2 h, 5.42±0.50 6.36±0.70 p<0.01 at 3 h, respectively). The other trials21,26 only gave graphics but not data on asthma score. One study21 reported a significantly reduction in the clinical score for the budesonide, but the other26 did not.
b. LOS in ED studies: Three studies20,25,28 reported data for this outcome. There was not significantly difference in LOS between the budesonide and control groups MD= -0.26 [-0.88 to 0.35]; I2= 91%, p=0.40).
c. Readmissions during follow-up: Four studies20,21,23,25 included data for this outcome. There was no significant difference in readmission during the follow-up (overall OR=0.89 [0.36 to 2.25]; I2 = 0%, p=0.81).
d. Lung function: Only two studies22,24reported this outcome and both measured the peak expiratory flow rate (PEFR). Nuhoglu et al.22 reported an increased mean of PEFR in the budesonide vs. placebo group (72.50 ± 23.8 vs. 47.86 ± 18.9, p=0.02). Similarly, Akhtaruzzaman et al.24 reported significantly more improvement in the % of predicted PEFR value in the budesonide vs. placebo group at 1,2 and 3 hour after treatment (76.63 ± 1.4 vs. 69.30 ± 1.1, p=<0.01; 77.42 ± 1.2 vs. 71.42 ± 1.1, p=<0.01; and 78.58 ± 1.1 vs. 72.36 ± 1.0, p=<0.01, respectively).
e. SpO2: Four studies done in ED20, 23,27,28 reported data for this outcome. The pooled data of two studies23,27 showed no difference in the mean change from baseline among budesonide vs. control group (data not shown). Similarly, Sung et al.20 reported no difference. However, Razi et al.28 showed significant higher SpO2 at 120 min post-intervention in the budesonide vs. placebo group (95% [93–98] vs. 91.5% [90–96], p=0.012).
Among studies performed in trials with hospitalized children, Akhtaruzzaman et al.24 found a significant difference at 1, 2, and 3 hrs. after intervention favorable for the budesonide vs. placebo group (95.15% ± 0.71 vs. 94.12% ± 0.89, p <0.01; 95.55% ± 0.71vs. 94.45% ± 0.83, p<0.01; and 95.94% ± 0.35 vs. 94.76% ± 0.66, p<0.01, respectively).
f. Heart and respiratory rates: Three studies20,23,28 done at ED and one in hospitalized children24reported data for heart rate. The pooled data of two ED studies23,28 showed no significant difference in overall heart rate change between the budesonide and control groups (MD = -1.08 [-6.48 to 4.32]; I2 = 0%, p=0.70). Also, Sung et al.20 reported that there were no differences between groups. The study performed in hospitalized children24 showed a significant lower heart rate at 1, 2, and 3 hrs. after intervention favorable to budesonide vs. placebo group (102.18±6.58 vs. 109.09±5.48, p <0.01; 88.42±5.36 vs. 96.85±5.24, p<0.01; 83.64±3.86 vs. 93.52±4.56, p<0.01, respectively).
Four studies21,23,24,27 reported data for the respiratory rate. There was no significant change in pooled data for respiratory rate among studies done in ED23,27 (MD = 0.43 [-1.43 to 2.29]; I2 = 0%, p=0.65). However, among trials with hospitalized children, Sano et al.21reported significantly higher respiratory rates at 24, 36, and 48 hrs. among children in the control group (who received ipratropium bromide) than those in the budesonide group; and Akhtaruzzaman et al.24 reported a significant lower respiratory rate at 1, 2, and 3 hrs. after intervention favorable to budesonide vs. placebo group (24.97±3.25 vs. 27.82±4.10, p <0.01; 23.55±2.77 vs. 25.27±3.35,p <0.01; and 22.42±1.79 vs. 24.48±2.74, p <0.01, respectively).
g. Additional SABA requirement: Only one study20 reported this outcome, showing no difference in additional salbutamol use between groups.
h. Adverse events: Six studies20,23-27reported AE data, and four studies20,24,26,27 reported no occurrence of AEs. Upham et al.23 reported a total of 106 AEs in 62 patients (33 in the budesonide and 29 in the control group). Alangari et al.25 described 28 AE episodes, 17 cases of fine tremors (7 in the budesonide and 10 in the control group), and 11 cases of palpitations (6 in the budesonide and 5 in the control group); these details were described in their protocol document (NCT01524198).